Johnson R W
Laboratory of Integrative Biology, 390 Animal Science Laboratory, Department of Animal Sciences, University of Illinois, 1207 West Gregory Drive, Urbana, IL 61801, USA.
Vet Immunol Immunopathol. 2002 Sep 10;87(3-4):443-50. doi: 10.1016/s0165-2427(02)00069-7.
Neurons do not have receptors to detect bacteria or viruses, yet the presence of these microorganisms can cause a sickness behavior syndrome that includes, e.g., fever, anorexia, and lethargy. Because the immune system has receptors capable of detecting these non-cognitive stimuli, how the immune system transmits a message to the brain has been studied to understand why behavior is altered in sick animals. The focus has been on several cytokines secreted by leukocytes; these include interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). These cytokines are secreted by activated mononuclear phagocytic cells, and numerous studies show that both peripheral and central injection of IL-1beta, IL-6, and TNF-alpha induce sickness behavior. Moreover, these cytokines and their receptors are present in the brain and inhibiting the secretion of cytokines or blocking their receptors in the brain blocks or abrogate the behavioral responses induced by inflammatory stimuli. Because the sickness behavior syndrome modulates the immune system and enhances recovery, the interplay between the immune system and central nervous system is an essential part of the overall host defense against pathogenic microorganisms. The purpose of this brief paper is to provide a chronological description of four critical advances that have led to the current understanding of how the immune system communicates with the brain to induce sickness behavior. Results from several key studies will be discussed, which showed that: (1) sickness behavior is a motivational state; (2) sickness behavior is a well-organized adaptive response to infection; (3) cytokines produced by activated leukocytes induce sickness behavior; and (4) cytokines transmit messages from the periphery to the brain using humoral and neural pathways.
神经元没有检测细菌或病毒的受体，但这些微生物的存在会引发一种疾病行为综合征，包括例如发烧、厌食和嗜睡。由于免疫系统具有能够检测这些非认知刺激的受体，因此人们研究了免疫系统如何向大脑传递信息，以了解患病动物的行为为何会发生改变。研究重点一直放在白细胞分泌的几种细胞因子上；这些细胞因子包括白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α（TNF-α）。这些细胞因子由活化的单核吞噬细胞分泌，大量研究表明，外周和中枢注射IL-1β、IL-6和TNF-α都会诱发疾病行为。此外，这些细胞因子及其受体存在于大脑中，抑制细胞因子的分泌或阻断其在大脑中的受体，会阻断或消除炎症刺激诱导的行为反应。由于疾病行为综合征会调节免疫系统并促进恢复，因此免疫系统与中枢神经系统之间的相互作用是宿主整体防御病原微生物的重要组成部分。本短文的目的是按时间顺序描述四项关键进展，这些进展促成了我们目前对免疫系统如何与大脑通信以诱发疾病行为的理解。将讨论几项关键研究的结果，这些结果表明：（1）疾病行为是一种动机状态；（2）疾病行为是对感染的一种组织良好的适应性反应；（3）活化白细胞产生的细胞因子诱发疾病行为；（4）细胞因子利用体液和神经途径将信息从外周传递到大脑。
